EP0207882B1 - Use of terguride for the manufacture of a medicament for the treatment of geriatric infirmities - Google Patents
Use of terguride for the manufacture of a medicament for the treatment of geriatric infirmities Download PDFInfo
- Publication number
- EP0207882B1 EP0207882B1 EP86730096A EP86730096A EP0207882B1 EP 0207882 B1 EP0207882 B1 EP 0207882B1 EP 86730096 A EP86730096 A EP 86730096A EP 86730096 A EP86730096 A EP 86730096A EP 0207882 B1 EP0207882 B1 EP 0207882B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- terguride
- treatment
- dopamine
- geriatric
- medicament
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Definitions
- the invention relates to the use of terguride or its physiologically tolerable salts for the manufacture of a medicament for the treatment of geriatric complaints with the exception of Parkinson's disease.
- Suitable physiologically acceptable salts are salts of terguride with inorganic and organic acids.
- hydrochloric acid, phosphoric acid, sulfuric acid, methanesulfonic acid, glucoheptanoic acid, succinic acid, tartaric acid, maleic acid, etc. are suitable for salt formation.
- a preferred salt is the terguride dihydrogen phosphate.
- Terguride (6-methylergolin-8 ⁇ -yl) -1.1-diethylurea) itself and its nidation- and lactation-inhibiting as well as its antipsychotic effect when used orally on animals and humans due to its partial agonizing effect on dopamine receptors are known (DE PS 22 38 540, DE OS 31 29 714).
- Parkinson's disease has been known for a long time, for the therapy of which dopamine agonists such as L-dopa and bromocriptine have proven successful.
- this weakly active dopamine agonist has the disadvantage that its pronounced ⁇ -adrenolytic effect prohibits the use of higher doses as would be necessary in order to quickly achieve a stronger therapeutic effect.
- An acutely higher dosage of dihydroergotoxin is not possible, since in addition to the reduction in blood pressure mediated by dopaminerg, strong orthostatic reactions then occur.
- the object of the present invention was to provide an agent for the treatment of geriatric complaints, which for the treatment of those limited by the Dopamine function in old age is one of the causes of restrictions in vigilance, mood and psychomotor functions.
- terguride influences the dopaminergic neurotransmission in different ways under different initial conditions. This is how a dopamine hypofunction - e.g. by chronic reserpine administration in the rat or in Parkinson's disease - compensate by terguride, while intact dopamine systems are not influenced by comparable doses. The side effects are therefore less and symptoms such as those observed by stimulating the dopamine receptor with classic dopamine agonists are not to be expected. Systems with hyperactive dopamine are even possible - e.g. by amphetamine or lisuride treatment in rats or Huntington's disease or schizophrenia - by terguride, without affecting other dopaminergic systems with normal function. It was therefore not foreseeable that terguride could be used as a partial dopamine agonist for the treatment of underactive dopamine and also for the treatment of overactive dopamine.
- terguride is better tolerated compared to bromocriptine. Compared to hydergin, terguride is more effective, although the effects are even faster. The use of terguride causes fewer orthostasis problems compared to the use of the two standard substances.
- terguride in comparison to the existing therapeutic options with strong dopamine agonists and their strong side effects on the one hand and the weak dopamine agonist dihydroergotoxin with strong ⁇ -adrenolytic component and to a lesser and later effect (Loew et al., Aging 23 , 227-239, 1983 ) means the treatment of Cerebral insufficiency in old age and other consequences of a functional dopamine deficiency, with terguride a significant improvement.
- drugs based on terguride can be administered orally or patenterally, such as subcutaneously, intramuscularly and intravenously. Oral application is preferred.
- the daily dose is 0.1-5.0 mg, preferably 0.25-1.0 mg.
- the pharmaceutical specialties are produced in a manner known per se, in that the terguride is processed with the carrier substances, diluents, flavoring agents, etc. customary in pharmacy.
- aqueous, but also oily solutions and suspensions are suitable for injections.
- the active substances can be suspended or dissolved in fatty oils according to common methods.
- Terguride can also be used in galenical preparations which are customary for the maintenance of uniform plasma levels, e.g. for continuous infusion with common pumps in aqueous or other suitable solvents in a dose of 0.01 - 10 mg / kg.
- Other substances such as dopamine agonists can be added to the oral and parental formulations in order to increase the effect or reduce side effects.
- the medicaments according to the invention are particularly suitable in the form of tablets, capsules, coated tablets, pills, suspensions and solutions for oral administration.
- Oral prolonged-release forms are also suitable, which are used in the usual way, e.g. by adding hydrogenated fats and processing with resin formers and varnishes.
- Drops for oral administration can be produced by aqueous solutions or suspensions of the active ingredient in oils with the addition of taste correctors and / or solubilizers.
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Led Device Packages (AREA)
- Prostheses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Lubricants (AREA)
Abstract
Description
Die Erfindung betrifft die Verwendung von Tergurid oder dessen physiologisch verträglichen Salzen zur Herstellung eines Arzneimittels zur Behandlung geriatrischer Beschwerden mit Ausnahme des Morbus Parkinson.The invention relates to the use of terguride or its physiologically tolerable salts for the manufacture of a medicament for the treatment of geriatric complaints with the exception of Parkinson's disease.
Als physiologisch verträgliche Salze kommen Salze von Tergurid mit anorganischen und organischen Säuren in Frage. Zur Salzbildung geeignet sind zum Beispiel Salzsäure, Phosphorsäure, Schwefelsäure, Methansulfonsäure, Glucoheptansäure, Bernsteinsäure, Weinsäure, Maleinsäure usw. Ein bevorzugtes Salz ist das Tergurid-dihydrogenphosphat.Suitable physiologically acceptable salts are salts of terguride with inorganic and organic acids. For example, hydrochloric acid, phosphoric acid, sulfuric acid, methanesulfonic acid, glucoheptanoic acid, succinic acid, tartaric acid, maleic acid, etc. are suitable for salt formation. A preferred salt is the terguride dihydrogen phosphate.
Tergurid (3-(6-Methylergolin-8α-yl)-1.1-diethylharnstoff) selbst und dessen nidations- und laktationshemmende sowie dessen antipsychotische Wirkung bei oraler Anwendung am Tier und am Menschen aufgrund seiner partialagonistischen Wirkung an Dopaminrezeptoren sind bekannt (DE PS 22 38 540, DE OS 31 29 714).Terguride (3- (6-methylergolin-8α-yl) -1.1-diethylurea) itself and its nidation- and lactation-inhibiting as well as its antipsychotic effect when used orally on animals and humans due to its partial agonizing effect on dopamine receptors are known (DE PS 22 38 540, DE OS 31 29 714).
Weiterhin sind auch verschiedene Mutterkornalkaloide, wie z.B. Bromocriptin oder Lisurid, in der Humanmedizin zur Hochdrucktherapie verwendet worden (Stumpe, K.O., Kolloch,R., Higuchi, M.K., Kruck, F., Vetter, H.: Hyperprolactinemia and antihypertensive effect of bromocryptine in essential hypertension, Lancet 2:211, 1977).Various ergot alkaloids, such as Bromocriptine or Lisurid, have been used in human medicine for high pressure therapy (Stumpe, KO, Kolloch, R., Higuchi, MK, Kruck, F., Vetter, H .: Hyperprolactinemia and antihypertensive effect of bromocryptine in essential hypertension, Lancet 2: 211, 1977).
Des weiteren ist bekannt, daß der für motorische, aber auch psychische, cognitive und endokrine Funktionen wichtige Neurotransmitter Dopamin mit zunehmendem Alter sowohl am Versuchstier als auch beim Menschen in seiner Konzentration im Gehirn und mit zunehmendem Alter in seiner Wirksamkeit abfällt (A. Carlsson and Winblad, B., J. Neural Transmission 38, 271-276, 1976; Severson, J.A. and Finch, C.E., Brain Research 192, 147-162, 1980). Als Extremform des Dopaminmangels im motorischen System ist seit langem der Morbus Parkinson bekannt, für dessen Therapie sich Dopaminagonisten wie L-Dopa und Bromocriptin bewährt haben.Furthermore, it is known that the neurotransmitter dopamine, which is important for motor, but also psychological, cognitive and endocrine functions, decreases with increasing age both in the test animal and in humans in its concentration in the brain and with increasing age in its effectiveness (A. Carlsson and Winblad , B., J. Neural Transmission 38, 271-276, 1976; Severson, JA and Finch, CE, Brain Research 192, 147-162, 1980). As an extreme form Due to the lack of dopamine in the motor system, Parkinson's disease has been known for a long time, for the therapy of which dopamine agonists such as L-dopa and bromocriptine have proven successful.
Diese Substanzen haben jedoch den Nachteil, daß sie derart stark auf alle Dopaminrezeptoren wirken, daß sie als Nebenwirkung auch Übelkeit, Erbrechen, orthostatische Dysregulation und Benommenheit hervorrufen.However, these substances have the disadvantage that they act so strongly on all dopamine receptors that they also cause nausea, vomiting, orthostatic dysregulation and drowsiness as a side effect.
Die Anwendung anderer Mutterkornalkaloide mit schwach dopaminerger Wirksamkeit - die erst bei einer Langzeitbehandlung, z.B. als Prolaktinsenkung feststellbar ist - wie das Dihydroergotoxin, das zur Therapie für cognitive und Vigilanzstörungen sowie anderer Störungen der Hirnfunktion im Alter eingesetzt werden kann, ist ebenfalls bekannt (R.J. McDonald, Pharmacopsychiatry 12, 407-422, 1979).The use of other ergot alkaloids with weak dopaminergic activity - which can only be determined with long-term treatment, e.g. as a prolactin reduction - such as dihydroergotoxin, which can be used for therapy for cognitive and vigilance disorders and other disorders of brain function in old age, is also known (RJ McDonald, Pharmacopsychiatry 12 , 407-422, 1979).
Dieser schwach wirksame Dopaminagonist hat jedoch den Nachteil, daß seine ausgeprägte α-adrenolytische Wirkung die Anwendung höherer Dosierungen, wie sie nötig wären, um rasch eine stärkere therapeutische Wirkung zu erreichen, verbietet. Eine akut höhere Dosierung von Dihydroergotoxin ist nicht möglich, da dann neben der dopaminerg vermittelten Blutdrucksenkung starke orthostatische Reaktionen auftreten.However, this weakly active dopamine agonist has the disadvantage that its pronounced α-adrenolytic effect prohibits the use of higher doses as would be necessary in order to quickly achieve a stronger therapeutic effect. An acutely higher dosage of dihydroergotoxin is not possible, since in addition to the reduction in blood pressure mediated by dopaminerg, strong orthostatic reactions then occur.
Die Aufgabe der vorliegenden Erfindung war es, ein Mittel zur Behandlung von geriatrischen Beschwerden bereitzustellen, welches zur Behandlung der durch die eingeschränkte Dopaminfunktion im Alter mitverursachten Einschränkungen von Vigilanz, Stimmung und psychomotorischen Funktionen geeignet ist.The object of the present invention was to provide an agent for the treatment of geriatric complaints, which for the treatment of those limited by the Dopamine function in old age is one of the causes of restrictions in vigilance, mood and psychomotor functions.
Es wurde überraschenderweise gefunden, daß Tergurid bei unterschiedlichen Ausgangsbedingungen die dopaminerge Neurotransmission in unterschiedlicher Weise beeinflußt. So läßt sich eine Dopaminunterfunktion - z.B. durch chronische Reserpingabe in der Ratte oder beim Morbus Parkinson - durch Tergurid ausgleichen, während intakte Dopaminsysteme durch vergleichbare Dosierungen nicht beeinflußt werden. Daher sind die Nebenwirkungen geringer und Symptome wie sie durch Stimulation des Dopaminrezeptors mit klassischen Dopaminagonisten beoabachtet werden, sind nicht zu erwarten. Es ist sogar möglich Systeme mit Dopaminüberfunktion - z.B. durch Amphetamin- oder Lisuridbehandlung an der Ratte oder beim Morbus Huntington oder Schizophrenie - durch Tergurid zu hemmen, ohne daß andere dopaminerge Systeme mit normaler Funktion beeinflußt werden. Es war daher nicht vorhersehbar, daß Tergurid als Partialdopaminagonist zur Behandlung von Dopaminunterfunktion und auch zur Behandlung von Dopaminüberfunktion verwendet werden kann.It has surprisingly been found that terguride influences the dopaminergic neurotransmission in different ways under different initial conditions. This is how a dopamine hypofunction - e.g. by chronic reserpine administration in the rat or in Parkinson's disease - compensate by terguride, while intact dopamine systems are not influenced by comparable doses. The side effects are therefore less and symptoms such as those observed by stimulating the dopamine receptor with classic dopamine agonists are not to be expected. Systems with hyperactive dopamine are even possible - e.g. by amphetamine or lisuride treatment in rats or Huntington's disease or schizophrenia - by terguride, without affecting other dopaminergic systems with normal function. It was therefore not foreseeable that terguride could be used as a partial dopamine agonist for the treatment of underactive dopamine and also for the treatment of overactive dopamine.
Somit ist die Anwendung von Tergurid bei Cerebralinsuffizienz im Alter, Unterfunktion dopaminerger Systeme, zur Regulierung der Motorik, Stimmung und Vigilanz möglich, ohne daß hierdurch - wie im Falle der klassischen Dopaminagonisten - schwer erträgliche subjektive Nebenwirkungen ausgelöst werden. Die zusätzliche Möglichkeit auch Dopaminüberfunktion zu normalisieren, ist auch nützlich, wenn die Überfunktion durch dopaminerge Arzneimittel ausgelöst wurde, z.B. bei Morbus Parkinson.Thus, the use of terguride in cerebral insufficiency in old age, underfunction of dopaminergic systems, to regulate motor skills, mood and vigilance is possible without triggering - as in the case of the classic dopamine agonists - subjective effects that are difficult to tolerate. The additional possibility of also normalizing dopamine hyperfunction is also useful if the hyperfunction was triggered by dopaminergic drugs, e.g. in Parkinson's disease.
Klinisch zeigte sich in kontrollierten Studien bei alten Patienten mit Morbus Parkinson durch eine Behandlung mit Tergurid nicht nur eine Verbesserung der Motorik, sondern zugleich auch der Stimmung und Vigilanz. Bei Patienten mit den klinischen Zeichen einer Demenz ließen sich im Elektroencephalogramm (EEG)
Frequenzveränderungen nachweisen, die den mit dem Altern verbundenen EEG-Frequenzänderungen entgegenliefen.Clinically, controlled studies in older patients with Parkinson's disease showed not only an improvement in motor skills but also mood and vigilance through treatment with terguride. In patients with the clinical signs of dementia, the electroencephalogram (EEG)
Detect frequency changes that ran counter to the EEG frequency changes associated with aging.
Bei alten Probanden , die gleichzeitig an Hochdruck litten, wurden die allgemeine Leistungsfähigkeit und das Wohlbefinden durch eine Reduktion des erhöhten systolischen und diastolischen Blutdrucks nicht beeinträchtigt. Eine schonende, langsam sich entwickelnde antihypertensive Wirkung ohne gleichzeitig auftretende Änderungen der Herzfrequenz trägt darüberhinaus dazu bei, die durch Hypertonie bedingten Gefäßkomplikationen zu reduzieren.In elderly subjects who suffered from high pressure at the same time, general performance and well-being were not impaired by a reduction in increased systolic and diastolic blood pressure. A gentle, slowly developing antihypertensive effect without simultaneous changes in the heart rate also helps to reduce the vascular complications caused by hypertension.
In allen Fällen und im Gegensatz zur Therapie mit Dopaminagonisten waren die subjektive und objektive Verträglichkeit von Tergurid sehr gut. Im Gegensatz zur sonstigen Therapie ließen sich die positiven Aspekte der Behandlung bereits in den ersten Tagen feststellen.In all cases and in contrast to therapy with dopamine agonists, the subjective and objective tolerability of terguride was very good. In contrast to other therapy, the positive aspects of the treatment could be determined in the first few days.
Eine sofortige dopaminerge Stimulation durch Tergurid ließ sich auch durch die prolaktinsenkende Wirkung dieser Behandlung zeigen. Ein Effekt, der nach der Behandlung mit Dihydroergotoxin erst nach Wochen oder Monaten eintritt und dann mit dem klinischen Therapieerfolg bei Cerebralinsuffizienz im Alter korreliert ist. Orthostatische Dysregulationen werden in den verabreichten Dosierungen nicht beobachtet.Immediate dopaminergic stimulation by terguride was also demonstrated by the prolactin-lowering effects of this treatment. An effect that occurs after weeks or months after treatment with dihydroergotoxin and is then correlated with the clinical success of therapy for cerebral insufficiency in old age. Orthostatic dysregulations are not observed in the doses administered.
Die klinischen Ergebnisse sind in der nachfolgenden Tabelle dargestellt.
(+) sehr selten beobachtet (bei höheren Dosen)
+ vorhanden (aber meist bei höheren Dosen)
++ ausgeprägt bei normalen Dosisbereichen
(+) observed very rarely (at higher doses)
+ available (but mostly at higher doses)
++ pronounced in normal dose ranges
Die Daten in der Tabelle zeigen, daß Tergurid im Vergleich zu Bromocriptin besser verträglich ist. Im Vergleich zum Hydergin ist Tergurid stärker wirksam, wobei die Wirkung auch noch rascher eintritt. Die Anwendung von Tergurid bereitet im Vergleich zur Anwendung der beiden Standardsubstanzen weniger Orthostase-Probleme.The data in the table show that terguride is better tolerated compared to bromocriptine. Compared to hydergin, terguride is more effective, although the effects are even faster. The use of terguride causes fewer orthostasis problems compared to the use of the two standard substances.
Die erfindungsgemäße Verwendung von Tergurid im Vergleich zu den vorhandenen Therapiemöglichkeiten mit starken Dopaminagonisten und ihren starken Nebenwirkungen einerseits und dem schwachen Dopaminagonisten Dihydroergotoxin mit starker α-adrenolytischer Komponente und zu geringer und später Wirkung (Loew et al., Aging 23, 227-239, 1983) bedeutet bei einer Behandlung der Cerebralinsuffizienz im Alter und anderer Folgen eines funktionellen Dopaminmangels, mit Tergurid somit eine erhebliche Verbesserung.The use of terguride according to the invention in comparison to the existing therapeutic options with strong dopamine agonists and their strong side effects on the one hand and the weak dopamine agonist dihydroergotoxin with strong α-adrenolytic component and to a lesser and later effect (Loew et al., Aging 23 , 227-239, 1983 ) means the treatment of Cerebral insufficiency in old age and other consequences of a functional dopamine deficiency, with terguride a significant improvement.
In der medizinischen Praxis können Arzneimittel auf Basis von Tergurid per oral oder patenteral wie subcutan, intramuskulär und intravenös appliziert werden. Bevorzugt ist die per orale Applikation. Die tägliche Dosis beträgt 0,1 - 5,0 mg, bevorzugt 0,25 - 1,0 mg.In medical practice, drugs based on terguride can be administered orally or patenterally, such as subcutaneously, intramuscularly and intravenously. Oral application is preferred. The daily dose is 0.1-5.0 mg, preferably 0.25-1.0 mg.
Die Herstellung der Arzneimittelspezialitäten erfolgt in an sich bekannter Weise, indem das Tergurid mit den in der Pharmazie gebräuchlichen Trägersubstanzen, Verdünnungsmitteln, Geschmackskorrigentien usw. verarbeitet wird. Für Injektionen kommen insbesondere wässrige, aber auch ölige Lösungen sowie Suspensionen in Frage. Zur Herstellung intramuskulärer Depotformen können die Wirkstoffe nach gängigen Methoden in fetten Ölen suspendiert oder gelöst werden.The pharmaceutical specialties are produced in a manner known per se, in that the terguride is processed with the carrier substances, diluents, flavoring agents, etc. customary in pharmacy. In particular, aqueous, but also oily solutions and suspensions are suitable for injections. For the production of intramuscular depot forms, the active substances can be suspended or dissolved in fatty oils according to common methods.
Tergurid kann auch in für die Erhaltung von gleichmäßigen Plasmaspiegeln üblichen galenischen Zubereitungen verwendet werden wie z.B. für die Dauerinfusion mit gebräuchlichen Pumpen in wässrigen oder anderen geeigneten Lösungsmitteln in einer Dosis von 0,01 - 10 mg/kg. Den oralen und parentalen Formulierungen können andere Stoffe wie beispielsweise Dopaminagonisten zugesetzt werden, um die Wirkung zu erhöhen oder Nebenwirkungen zu verringern .Terguride can also be used in galenical preparations which are customary for the maintenance of uniform plasma levels, e.g. for continuous infusion with common pumps in aqueous or other suitable solvents in a dose of 0.01 - 10 mg / kg. Other substances such as dopamine agonists can be added to the oral and parental formulations in order to increase the effect or reduce side effects.
Die erfindungsgemäßen Arzneimittel sind insbesondere in Form von Tabletten, Kapseln, Dragees, Pillen, Suspensionen und Lösungen für die orale Applikation geeignet. Geeignet sind aber auch orale Retardformen, die in üblicher Weise, z.B. durch Zugabe von hydrierten Fetten und Verarbeitung mit Harzbildnern und Lacken, erhalten werden. Tropfen für die orale Applikation können durch wässrige Lösungen oder Suspensionen des Wirkstoffes in Ölen unter Zugabe von Geschmackskorrigenten und/oder Lösungsvermittlern hergestellt werden.The medicaments according to the invention are particularly suitable in the form of tablets, capsules, coated tablets, pills, suspensions and solutions for oral administration. Oral prolonged-release forms are also suitable, which are used in the usual way, e.g. by adding hydrogenated fats and processing with resin formers and varnishes. Drops for oral administration can be produced by aqueous solutions or suspensions of the active ingredient in oils with the addition of taste correctors and / or solubilizers.
Claims (4)
- Use of terguride or the physiologically tolerable salts thereof for the preparation of a medicament for the treatment of geriatric complaints, with the exception of Parkinson's disease.
- Use according to claim 1, characterised in that cognitive and psychic disorders are treated.
- Use according to claim 1, characterised in that limitations of mood, attentiveness, of psychomotor functions and cerebral insufficiency are treated.
- Use according to claim 2, characterised in that dementia is treated.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19853522894 DE3522894A1 (en) | 1985-06-24 | 1985-06-24 | USE OF TERGURID AS GERIATRIC |
| DE3522894 | 1985-06-24 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| EP0207882A2 EP0207882A2 (en) | 1987-01-07 |
| EP0207882A3 EP0207882A3 (en) | 1990-01-31 |
| EP0207882B1 true EP0207882B1 (en) | 1997-01-02 |
Family
ID=6274270
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP86730096A Expired - Lifetime EP0207882B1 (en) | 1985-06-24 | 1986-06-20 | Use of terguride for the manufacture of a medicament for the treatment of geriatric infirmities |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4711891A (en) |
| EP (1) | EP0207882B1 (en) |
| JP (1) | JP2618375B2 (en) |
| AT (1) | ATE146963T1 (en) |
| AU (1) | AU573448B2 (en) |
| CA (1) | CA1285880C (en) |
| DE (2) | DE3522894A1 (en) |
| DK (1) | DK288786A (en) |
| IE (1) | IE80545B1 (en) |
| IL (1) | IL79207A (en) |
| ZA (1) | ZA864717B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10226459A1 (en) * | 2002-06-13 | 2004-01-08 | Neurobiotec Gmbh | Use of dopamine partial agonists to treat restless legs syndrome |
| EP2067780A1 (en) * | 2007-12-07 | 2009-06-10 | Axxonis Pharma AG | Ergoline derivatives as selective radical scavengers for neurons |
| LU92975B1 (en) * | 2016-02-09 | 2017-08-10 | Vivotecc Gmbh | Use of Lisuride and Terguride and its 2-Halogen Derivatives for the Treatment as Antipsychotics |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0056358A1 (en) * | 1981-01-14 | 1982-07-21 | Schering Aktiengesellschaft | Novel (2-haloergolinyl)-N'-N'-diethylurea derivatives, process for the preparation thereof, and use thereof as medicinal agents |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH573936A5 (en) * | 1971-08-05 | 1976-03-31 | Spofa Vereinigte Pharma Werke | |
| US4323546A (en) * | 1978-05-22 | 1982-04-06 | Nuc Med Inc. | Method and composition for cancer detection in humans |
| DE3063869D1 (en) * | 1979-06-13 | 1983-07-28 | Schering Ag | (ergolin-yl)-n', n'-diethyl urea derivatives, their preparation and pharmaceutical compositions containing them |
| JPS5732281A (en) * | 1980-08-06 | 1982-02-20 | Sumitomo Chem Co Ltd | Nitrogen-containing polycyclic compound and its preparation |
| CS231214B1 (en) * | 1982-03-12 | 1984-10-15 | Antonin Cerny | Processing method of 1-substituted n+l8alpha-ergoline+p-n,diethyl urea |
| DE3309493A1 (en) * | 1983-03-14 | 1984-09-20 | Schering AG, 1000 Berlin und 4709 Bergkamen | NEW ERGOLIN DERIVATIVES, PROCESS FOR THEIR PRODUCTION AND USE AS A MEDICINAL PRODUCT |
| DE3410218A1 (en) * | 1984-03-16 | 1985-09-19 | Schering AG, Berlin und Bergkamen, 1000 Berlin | TERGURID AS AN ANTI-HYPERTENSIVE |
| US4552820A (en) * | 1984-04-25 | 1985-11-12 | Lin Data Corporation | Disc media |
-
1985
- 1985-06-24 DE DE19853522894 patent/DE3522894A1/en not_active Ceased
-
1986
- 1986-06-10 US US06/872,779 patent/US4711891A/en not_active Expired - Fee Related
- 1986-06-19 DK DK288786A patent/DK288786A/en not_active Application Discontinuation
- 1986-06-20 DE DE3650590T patent/DE3650590D1/en not_active Expired - Lifetime
- 1986-06-20 EP EP86730096A patent/EP0207882B1/en not_active Expired - Lifetime
- 1986-06-20 AT AT86730096T patent/ATE146963T1/en not_active IP Right Cessation
- 1986-06-23 AU AU59206/86A patent/AU573448B2/en not_active Ceased
- 1986-06-23 IE IE166386A patent/IE80545B1/en not_active IP Right Cessation
- 1986-06-23 JP JP61145028A patent/JP2618375B2/en not_active Expired - Lifetime
- 1986-06-23 CA CA000512215A patent/CA1285880C/en not_active Expired - Lifetime
- 1986-06-24 ZA ZA864717A patent/ZA864717B/en unknown
- 1986-06-24 IL IL79207A patent/IL79207A/en not_active IP Right Cessation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0056358A1 (en) * | 1981-01-14 | 1982-07-21 | Schering Aktiengesellschaft | Novel (2-haloergolinyl)-N'-N'-diethylurea derivatives, process for the preparation thereof, and use thereof as medicinal agents |
Non-Patent Citations (11)
| Title |
|---|
| ADVANCES IN NEUROLOGY, Band 45, 8th Int. Symp. Parkinson's Disease, 9-12. Juni 1985, Seiten 577-582, Raven Press, New York, US; I. SUCHY et al.: "Evaluation of terguride in patients with Parkinson's disease" * |
| ADVANCES IN NEUROLOGY, Band 45, 8th Int. Symp. Parkinson's Disease, 9-12. Juni, 1985, S. 573-576, Raven Press, New York, US; T. BRÜCKE et al.: "Terguride: partial dopamine agonist in the treatment of Parkinson's disease" * |
| Allgemeine und Spezielle Pharmakologie und Toxikologie, S. 569-572 * |
| CLIN. NEUROPHARMACOL., Band 7, Suppl. 1, 1984, Seiten 950-951; Raven Press, New York, US G.U. CORSINI et al.: "Treatment of Parkinson's disease with a dopamine partial agonist" * |
| Dorland's Illustrated Medical Dictionary, 28. Auflage, 1981, Seite547 * |
| J. NEUROL., Band 232, Suppl. 1985, Seite 163, Ref. Nr. 11.21.02; M. ESTEGUY et al.: "Treatment of Parkinson's disease with transdihydrolisuride" * |
| LIFE SCIENCE, Band 32, 1983, Seiten 421-432, Pergamon Press, US; H. WACHTEL et al.: "Dual action on central dopamine function of transdiydrolisuride, A9,10- dihydrogenated analogue of the Ercodopamine agonist lisuride" * |
| Pschyrembel Klinisches Wörterbuch, 1977, S. 1113 * |
| Römpps Chemie-Lexikon, 8. Auflage, 1981, S.1453 * |
| The Merck Manual, 14. Auflage, 1982, Seiten 1360 und 2226 * |
| THE MERCK MANUAL, Band 14, 1982, S. 1359-1362, 1462-1471; Ed. R. BERKOW, Merck & Co., Rahway, US * |
Also Published As
| Publication number | Publication date |
|---|---|
| DK288786D0 (en) | 1986-06-19 |
| IL79207A0 (en) | 1986-09-30 |
| DE3650590D1 (en) | 1997-02-13 |
| AU573448B2 (en) | 1988-06-09 |
| CA1285880C (en) | 1991-07-09 |
| IL79207A (en) | 1993-04-04 |
| IE80545B1 (en) | 1998-09-09 |
| ZA864717B (en) | 1987-02-25 |
| JPS6259211A (en) | 1987-03-14 |
| DK288786A (en) | 1986-12-25 |
| EP0207882A2 (en) | 1987-01-07 |
| AU5920686A (en) | 1987-01-08 |
| US4711891A (en) | 1987-12-08 |
| ATE146963T1 (en) | 1997-01-15 |
| JP2618375B2 (en) | 1997-06-11 |
| DE3522894A1 (en) | 1987-01-02 |
| EP0207882A3 (en) | 1990-01-31 |
| IE861663L (en) | 1986-12-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69929041T2 (en) | USE OF CABERGOLIN FOR THE TREATMENT OF "RESTLESS LEGS SYNDROME" | |
| DE2856393C2 (en) | Medicines used to treat Parkinson's disease | |
| EP2072054B1 (en) | Use of a ginkgo biloba leaf extract | |
| DE60218193T2 (en) | USE OF 2-OXO-1-PYRROLIDINE DERIVATIVES FOR THE PREPARATION OF A MEDICAMENT FOR THE TREATMENT OF DYSKINESIA | |
| CN110292573B (en) | Depression-relieving and sleep-aiding compound essential oil | |
| DE69829202T2 (en) | USE OF MIRTAZAPINE FOR THE MANUFACTURE OF A MEDICAMENT FOR THE TREATMENT OF SLEEP APNOES | |
| DE3511609C2 (en) | ||
| DE69635754T2 (en) | MEDICAMENTS FOR PREVENTING CONDITIONAL STENOSIS AS A RESULT OF NON-BYPASS INVASIVE INTERVENTION | |
| EP0207882B1 (en) | Use of terguride for the manufacture of a medicament for the treatment of geriatric infirmities | |
| DE2359128A1 (en) | MEDICINAL PRODUCTS BASED ON LISURIDE AND ITS PHYSIOLOGICALLY COMPATIBLE SALT | |
| EP0618797B1 (en) | Pharmaceutical preparations containing bilobalid for the treatment of nervous tension and anxiety | |
| DE60103685T2 (en) | Treatment of Poriomania | |
| EP0331014A2 (en) | Use of ACE inhibitors in diabetes prophylaxis | |
| DE10163667B4 (en) | Use of deoxypeganine for the treatment of clinical depression | |
| DE2611976A1 (en) | PHARMACEUTICAL PREPARATION FOR IMPROVEMENT AND RESTORATION OF DETERMINED CONDITIONS OF CONSCIOUSNESS | |
| EP0075823B1 (en) | Use of basically substituted phenylacetonitriles in the prophylactic treatment of illnesses | |
| EP0493861B1 (en) | Antidepressive composition containing nicotinamid-adenin-dinucleotide | |
| DE10226459A1 (en) | Use of dopamine partial agonists to treat restless legs syndrome | |
| DE3129714A1 (en) | ANTI-PSYCHOTIC | |
| CH710163A2 (en) | Bupropion used to treat multiple sclerosis. | |
| EP0398171A2 (en) | Use of imidazodiazepines in the treatment of neurological symptoms associated with circulatory disorders of the brain | |
| EP0523591A2 (en) | Use of a Kava extract and of its constituents | |
| DE60208336T2 (en) | COMBINATION OF ACTIVA WITH ALFUZOSINE AND APOMORPHINE | |
| DE4110620A1 (en) | Use of extract from Gingko biloba leaves - for treating sleep apnea, opt. co-administered with theophylline | |
| DD210277A5 (en) | PROCESS FOR THE PRODUCTION OF PHYSIOLOGICALLY ACTIVE PTEROCARPAN COMPOUNDS |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 19860630 |
|
| AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
| PUAL | Search report despatched |
Free format text: ORIGINAL CODE: 0009013 |
|
| AK | Designated contracting states |
Kind code of ref document: A3 Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
| 17Q | First examination report despatched |
Effective date: 19910207 |
|
| GRAG | Despatch of communication of intention to grant |
Free format text: ORIGINAL CODE: EPIDOS AGRA |
|
| GRAH | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOS IGRA |
|
| GRAH | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOS IGRA |
|
| GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
| AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
| REF | Corresponds to: |
Ref document number: 146963 Country of ref document: AT Date of ref document: 19970115 Kind code of ref document: T |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP |
|
| REF | Corresponds to: |
Ref document number: 3650590 Country of ref document: DE Date of ref document: 19970213 |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: NV Representative=s name: E. BLUM & CO. PATENTANWAELTE |
|
| ITF | It: translation for a ep patent filed |
Owner name: 0403;13MIFING. ZINI MARANESI & C. S.R.L. |
|
| ET | Fr: translation filed | ||
| GBT | Gb: translation of ep patent filed (gb section 77(6)(a)/1977) |
Effective date: 19970403 |
|
| PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
| 26N | No opposition filed | ||
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 19980508 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: AT Payment date: 19980513 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: SE Payment date: 19980518 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GB Payment date: 19980522 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: NL Payment date: 19980527 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DE Payment date: 19980528 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CH Payment date: 19980529 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: BE Payment date: 19980604 Year of fee payment: 13 |
|
| PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: LU Payment date: 19981021 Year of fee payment: 13 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: DE Free format text: LAPSE BECAUSE OF THE APPLICANT RENOUNCES Effective date: 19990430 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990620 Ref country code: GB Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990620 Ref country code: AT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990620 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SE Free format text: THE PATENT HAS BEEN ANNULLED BY A DECISION OF A NATIONAL AUTHORITY Effective date: 19990629 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990630 Ref country code: FR Free format text: THE PATENT HAS BEEN ANNULLED BY A DECISION OF A NATIONAL AUTHORITY Effective date: 19990630 Ref country code: CH Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990630 Ref country code: BE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19990630 |
|
| BERE | Be: lapsed |
Owner name: SCHERING A.G. Effective date: 19990630 |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: NL Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20000101 |
|
| GBPC | Gb: european patent ceased through non-payment of renewal fee |
Effective date: 19990620 |
|
| REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
| EUG | Se: european patent has lapsed |
Ref document number: 86730096.4 |
|
| NLV4 | Nl: lapsed or anulled due to non-payment of the annual fee |
Effective date: 20000101 |
|
| REG | Reference to a national code |
Ref country code: FR Ref legal event code: ST |
|
| PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20050620 |